LONDON, OntarioA Canadian study is evaluating the safety and efficacy
of single-agent capecitabine
(Xeloda) among patients with advanced colorectal cancer deemed unsuitable
for more aggressive treatment with bolus fluorouracil
(5-FU)/leucovorin/irinotecan (also known as CPT-11, Camptosar).

The nonrandomized, multicenter phase I/II trial is based on concerns
about the potential toxicity of the widely used bolus combination among
patients who are elderly or unfit, according to lead investigator Mark
Vincent, MD, associate professor of oncology, University of Western Ontario,
and staff oncologist, London Regional Cancer Center. He discussed his ASCO
paper (abstract 2366) in an interview with ONI.

The investigators chose to study patients who fit into three broad
categories: Those who were too ill or too old to be considered for
aggressive therapy, those who would have been specifically excluded from the
original trial of the IV bolus 5-FU/irinotecan regimen, and patient groups
that had not seemed to experience a survival benefit from the addition of
irinotecan.

These broad criteria translated into five patient subgroups:

Patients over age 65

Patients with an ECOG performance status of 1 or 2

Patients with an elevated lactic dehydrogenase (LDH) level

Patients who had undergone prior pelvic irradiation

Patients with abnormal liver function tests

Patients in these groups are being offered capecitabine at a dose of
1,000 mg/m² bid, Dr. Vincent said. However, trial investigators are not
required to enroll everyone over age 65 into the trial. A fit and otherwise
healthy 66-year-old, for example, would not be a candidate for the study.
Furthermore, the patient’s preferences are followed whenever possible, and
some prefer to defer use of irinotecan until second-line therapy.

Patients with an impaired performance status and those with an elevated
LDH level were selected because neither group seemed to reap the added
survival benefits of the irinotecan in the original 5-FU/irinotecan study,
Dr. Vincent said.

"There was a huge benefit to CPT-11 in fit people and in fit people
with a normal LDH, but less survival benefit for anybody else," he
noted. "It seemed reasonable to offer people with an elevated LDH a
more gentle treatment because a more aggressive treatment might not add
much."